- Home
- Conference Proceedings
- Qatar Foundation Annual Research Conference Proceedings
- Conference Proceeding
Qatar Foundation Annual Research Conference Proceedings Volume 2018 Issue 2
- Conference date: 19-20 Mar 2018
- Location: Qatar National Convention Center (QNCC), Doha, Qatar
- Volume number: 2018
- Published: 15 March 2018
61 - 80 of 82 results
-
-
Cerebral blood flow and autoregulation in acute TIA patients from a general hospital in Qatar
BACKGROUND The Arabian Gulf region is rapidly developing, with major changes in lifestyle that can increase the risk of cardiovascular diseases, including TIA and stroke. Stroke constitutes a major cause of morbidity and mortality in Qatar. Cerebral auto-regulation is an intrinsic protective mechanism guaranteeinghemodynamic integrity of cerebral circulation. It modulates cerebral blood flow(CBF) in order to meet regional perfusion demands despite variations in arterial blood pressure. Impaired cerebral auto-regulation is associated with poor functional and prognostic outcomes in patients with ischemic stroke. OBJECTIVES The study has two arms; one arm is a health improvement project conducted in Qatar with the aim of developing, establishing and maintaining an acute stroke database (registry) in Qatar. The second arm is an applied research project with the aim to correlate CBF and cerebral auto-regulation and microalbuminuria in TIA patients, and to assess the prognostic significance of such a correlation. Thus far, no physiologic or biochemical biomarker has been proven as an effective predictor of poor outcome in TIA patients. DESIGN / METHODS Fifty-six patients (35 men, mean age, 53.2 yrs) with acute TIAs or small strokes (TIAs with tissue evidence of infarction) were enrolled last year and evaluated with bilateral, simultaneous TCD studies of their MCAs CBF within 72 hrs of the indexed event. On best medical therapy, the patients were followed up at one year for outcomes measures of death, stroke and recurrent TIAs in an attempt to correlate them with the TCD parameters. RESULTS Fifteen healthy volunteers (mean age 30 years) were studied using voluntary breath-holding technique to provide the hypercapnia stimulus to effect cerebral auto regulation of CBF in their MCAs. Fifty TIA patients (mean age 53.7 yrs) had complete TCD studies and 48 were followed up to one year. Seven experienced symptoms or signs of a new cerebrovascular event (3 strokes and 3 recurrent TIAs) for an annual rate for cerebrovascular events of 14%. The average BHI for the respective groups were 0.9 ± 0.78 for the controls, 0.62 ± 1.1 for the TIA patients and 0.31 ± 0.85 for those who had cerebrovascular events on follow up. MCA TCD studies with BHIs in the TIA patient group with stroke or recurrent TIA at follow up showed a tendency towards abnormality as compared to healthy controls (p>0.05) CONCLUSION Preliminary results indicate the feasibility of TCD and BHI in acute evaluation of TIA patients for the purpose of prognosis and functional outcome. Further studies are necessary to confirm their clinical value. Calculating BHI has potential of a strong prognostic predictor of future cerebrovascular events. It could be used as an inexpensive non-invasive tool for the acute evaluation of TIA patients. Together with other neuroimaging studies it brings a real time neurophysiologic dimension to the assessment and possible prevention of stroke.
-
-
-
Smart wearable sensing platform with wireless communication and embedded processing for health monitoring applications
Authors: Younss AitMou, Menatollah Elgendy, Safiya Jan, Augusto Manuel Lucas, Almiqdad Elzein and Amine BermakDiabetic patients tend to develop plantar ulcers due to various factors related to their pathology. These factors include, but are not limited to, a lack of plantar sensation, a poor blood circulation, and feet deformities. The plantar ulcers can be managed and cured if detected at an early stage and appropriately treated. However, if not detected early, they can evolve to rich critical stages involving extreme curative strategies such as amputation. Accordingly, it is crucial to detect these ulcers at an early stage. A common strategy to prevent ulcers worsening is by increasing the patient's medical check frequency. Although beneficial, this therapeutic approach is time consuming and might not be a perfect solution for elderly patients, and patients with reduced locomotive abilities. Accordingly, various groups have oriented their work toward the development of smart shoes to monitor plantar physical parameters under various conditions [1-3]. Previous studies have focused on healthy foot pressure analysis and soft therapies. Moreover, none of these studies has developed a centralized data system. Accordingly, our present work aim to develop a user and mobile phone friendly wireless device that is specifically targeting patients with diabetes to prevent plantar ulcers from reaching the critical levels by early detection of peak pressure, temperature, and humidity. Moreover, to improve patient monitoring, collected data will be centralized in a global database. To the aim of our present work we employed Velostat (a.k.a. Linqstat) to acquire plantar pressure. Velostat is thin conductive material that was previously employed as pressure sensor. When combined with an array of conductive net, this material can act as an array of pressure-sensors. Accordingly, we built a 10 cell array to acquire pressure from 10 strategic plantar locations, namely: Medial Plantar; Lateral Plantar; Saphenous; Sural; Tibial. Plantar wounds are often associated with increased local temperature that reflects a local sub-dermal infection. To monitor the temperature alteration, we utilized a DHT11 module. The DHT11, is an ideal module for simultaneous measurement of both temperature and humidity. Wound infection is often accompanied by local swelling and bleeding, Hence, the humidity detection. To acquire and pre-process the raw data, we employed an ATMEL 8-bit Microcontroller (ATMEGA 2560). Given it's high pin count, this device allowed as to overcome adding multiplexers to handle the significant number of input signals (13). Thus, allowing us to reduce the prototype footprint. To secure an effective data transfer to the mobile phone, we have used an HC-06 as a Bluetooth transceiver. Once collected and sampled (1 Hz rate), the data is then transferred to the mobile phone trough the Bluetooth connection. For user convenience, the mobile application displays current values at 1 Hz frequency along with a time-stamp chart. When the temperature reaches a critical wound level (33-34°C)[4], the device sends a warning notification to the monitoring application that is held by the health-care processionals (i.e. nurses and doctors). In addition, wound maceration[5] and drying[6] notification warnings are detected and sent to the monitoring application. The later values are calculated based on the humidity sensor's raw data. The monitoring application pulls data from the server and evaluates the wound severity by combings all sensors' data. To centralize all collected data, and improve patient monitoring, the raw and analyzed data are stored in a global database that can be accessed from either a web application or the monitoring mobile phone application. Reference: 1. Bamberg, S.J.M., Benbasat A.Y., Scarborough D.M., Krebs D.E. Paradiso J.A. Gait Analysis Using a Shoe-Integrated Wireless Sensor System. IEEE Transactions on Information Technology in Biomedicine, Vol. 12, No. 4, July 2008, pp. 413-423.2. Paradiso, J.A., Morris, S.J., Benbasat, A.Y., Asmussen, E., «Interactive Therapy with Instrumented Footwear,» in the Proc. of the ACM Conference on Human Factors and Computing Systems (CHI 2004), Extended Abstracts, Vienna, Austria, April 27-29, 2004, pp. 1341-1343.3. Benbasat, A.Y., Morris, S.J, and Paradiso, J.A. «A Wireless Modular Sensor Architecture and its Application in On-Shoe Gait Analysis.» In the Proceedings of the 2003 IEEE International Conference on Sensors, October 21-24, Toronto, Ontario, pp. 1086-1091.4. Dini V, Salvo P, Janowska A, Di Francesco F, Barbini A, Romanelli M. Correlation Between Wound Temperature Obtained With an Infrared Camera and Clinical Wound Bed Score in Venous Leg Ulcers. Wounds 2015, Oct 15.5. K.F. Cutting, R.J. White. Maceration of the skin and wound bed. 1: Its nature and causes. J Wound Care, 11 (2002), pp. 275-278.6. G.D. Winter. Formation of the scab and the rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature, 193 (1962), pp. 293-294
-
-
-
Feasibility study of the use of mobile health for diabetes management in Qatar poster
Noor Suleiman1, Dabia Al Mohannadi1, Majed Lababidi2, Abdulla Al Misnad2, Mohammed Bashir1, Luis Luque3, Abdul Badi Abou-Samra1 Keywords: diabetes, mobile technology, internet, eHealth, smartphone, chronic condition Diabetes Mellitus (DM) is a chronic disease characterized by an elevated level of blood glucose and carries the risk of acute and chronic complications resulting in significant healthcare burden. DM has a high prevalence across many nations especially within the Middle East. In Qatar, DM prevalence in the adult population is approximately 16.7%. DM management is a well-known complex process that requires both lifestyle changes and effective pharmacologic treatment plans. To avoid DM complications, effective behavioral change, extensive education and promotion of appropriate self-management are key. Self-management tools are developing fast. Data recording of blood glucose and lifestyle changes have progressed from writing them on paper, to uploading them to computers, to recording them on mobile phones using traditional phone functions, and finally to using smartphone apps. Mobile health is becoming one of the fastest growing areas of effective healthcare delivery in many countries with health education and awareness programs being increasingly recognized as the key players. The surge of mobile healthcare (m-Health) in the last few years is due to the massive demand of such systems to alleviate and provide more efficient and effective healthcare delivery mechanisms especially for chronic disease management and self-care. Diabetes mobile technology is an emerging and rapidly expanding field that seeks to combine cutting edge behavioral insights with best practice in diabetes self-management education to improve patient empowerment and deliver better patient outcomes. However, there is a lack of research on the use of mobile technology to support diabetes self-management in the Arab world. The question that arises is whether or not, diabetes mobile applications are effective in improving glycemic control, clinical outcomes, quality of life and overall patient satisfaction, in diabetic patients in Qatar. We have the hypothesis that with utilization of the mobile application, patients will have improved diabetes knowledge, patient satisfaction and empowerment; glycemic control and diabetes outcomes; together with improved patient-educator/doctor interaction Qualitative research methods such as focus groups and interviews have been conducted among dozens of patients and health care professionals to identify strategies to design a patient-centered mobile application for diabetes, named droobi health. The main purpose of this application is to enhance patient care and improve clinical outcomes of diabetic patients through an active engagement with patients. Patients will have access to tools to monitor, manage and control their diabetes, enabling communication between patients and care providers while providing access to up-to-date diabetes educational materials. droobi health will provide a single source of patient self-management and lifestyle information for better collaboration between patient and care providers to positively interact and engage with the patient and personalize educational material when it is required. This app has the home-advantage of being created in Qatar for our particular patient population, taking into account the cultural adaptation and context, which is missing in the existing apps. We have completed the design based on feedback from healthcare providers and patients. Droobi provides a platform where the patient and his or her clinical care team can interact in order to address the patient's concerns in a timely manner. Additionally, Droobi aims to empower the patient towards implementing self-management together with providing robust education and training for the patients towards their disease resulting in increased knowledge and awareness. The feasibility of Droobi will be conducted in a small pilot, with its effectiveness later examined in a clinical trial. Hamad Medical Corporation Trio InvestmentsQatar Computing Research Institute
-
-
-
Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4hydroxynonenal in obese diabetic patients
Authors: Shamma Abdulla Almuraikhy, Mohamed Elrayess and Wael KafienahOBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. RESULTS: Preadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. CONCLUSION: This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.
-
-
-
A high carbohydrate diet increased adiposity and compromised vasodilation in rats
Authors: Hamda Aboujassoum, Nelson Orie, Lucie Clapp, Hamda Al-Naemi and Video Mohamed AliIntroduction Obesity is an epidemic problem that impairs human health. It can be defined as the accumulation of excessive body fat mass, leading to abnormal changes. The world is witness an explosion in the number of obesity cases. Worldwide obesity prevalence has more than doubled since 1980s as reported by World Health Organization (WHO). Indeed, the American Medical Association announced that obesity should be classified as a chronic disease. Qatar ranks sixth globally in the prevalence of obesity according to the International Association for the Study of Obesity. There are several causes considered to contribute in the development of obesity such as: genetics, health, diet and lifestyle. However, access to high energy-dense food, and physical inactivity makes a significant contribution to the increasing rate of obesity. Increasing body weight is closely associated with cardiovascular morbidity and mortality. It has a total impact on cardiovascular disease (CVDs) in the general population approximately equal to that of smoking. The relationship and the exact role by which obesity induces the cardiovascular risk are poorly investigated. This study aims to establish a diet-induced obesity rat model and to investigate the cardiovascular diseases risk factors associated with obesity. It also aimed to examine the effect of dietary weight loss on the reversibility of these risk factors. Methodology Male Sprague Dawly (SD) rats 8-9 weeks age old, were grouped into three categories: NC group fed with Normal chow (NC) and had access to regular water ad libitum, CAF group fed with a combination of cafeteria style diet (CAF) and normal chow with 5% sugar water ad libitum for 15 weeks, and reversibility group fed with CAF diet and NC ad libitum to induced weight gain and then switched to NC only for four weeks. The nutritional contents for each diet was: NC (49% CHO, 14.37% protein, 4.65% fat) and CAF (60-70% CHO, 9-12% protein, 10% fat). Body weight, food and water intake were measured weekly throughout the study. Blood was collected to test the changes in the metabolic parameters. Large vessels responsiveness was examined by using organ bath, in response to noradrenaline (NA) and acetylcholine (Ach). Results Results showed that CAF diet has an effect on body weight. All CAF fed-rats gained weight significantly with higher consumption of CAF diet compared to NC. A significant change in their lipid profile was also observed; it showed a significant increase in triglycerides and a decrease in HDL levels. In the reversible group, rats showed a slight weight loss of approximately 6% in 4 weeks. This weight loss was associated with a more favorable lipid profile; triglycerides and HDL returned to normal levels when CAF diet stopped. The vascular studies data suggests noradrenergic contractions in the CAF-fed group were muted compared with the control (NC-fed group). Similar effect was observed in the reversibility, when CAF diet stopped for 4 weeks. The Ach relaxation pattern suggests CAF feeding was associated with endothelial dysfunction. This effect was not reversed when the diet changed to normal chow. Conclusion In conclusion, this study developed a diet-induced obesity rat model with metabolic changes associated with obesity. It specifically examined the vascular changes caused by dietary weight gain and loss. Further investigations are in progress in order to investigate the mechanisms underlying these changes.
-
-
-
Prioritizing Access to the National Diabetes Center NDC Services Based on Clinical Need
Authors: Raissa Jacinto Puddao, Sara Darwish, Mariam Al-Malaheem and Mahmoud ZirieNDC is one of the busiest services at Hamad General Hospital (HGH) with 450-1000 new referrals monthly and an average waiting time of 84 days for an initial appointment. Triage guidelines from several government institutions in Canada, UK, and Australia stated that the patients with urgent conditions should be assessed within 2 weeks. Delaying urgent cases management poses a great patient safety risk that may endanger patient health and can lead to increased healthcare cost. In December 2016, a multidisciplinary team (physician, nurses, administration, and quality staff) was formed to pilot an urgent clinic service. The team standardized triaging criteria, calculated waste, and improved the process from triaging until the first appointment at NDC. Goal: To provide timely diagnosis and management for newly-referred patients to NDC who are considered urgent after physician's triage. Team Aim: To improve the percentage of referred patients with urgent cases who attended their initial consultation visit at the Diabetes-Endocrine Urgent Clinic within 2 weeks from physician's triage to 60% by May 2017. Methods: An urgent clinic exclusively for indicated urgent new referrals was piloted last December 2016. Fishbone diagram and process map were created. For testing changes, the Model for Improvement or Plan-Do-Study-Act (PDSA) was utilized. Several trials were done to identify the cases to be considered urgent during triage, manpower, clinic scheduling, appointment booking process, feedback gathering, and data collection. Results:For the past 9 months, there were 769 patients triaged to the urgent clinic. Around 65% of them were seen within 2 weeks, 12% no-show, and 23% were unable to attend due to various causes. We were able to surpass our goal for several months starting from January 2017 with the exemption in June 2017 when the clinic was closed for 10 days due to the Eid holidays.
-
-
-
Intermittent fasting during Ramadan causes transient loss of body fat and improvement in insulin sensitivity
Background. periods of voluntary abstinence from food, such as intermittent fasting, has been practiced since earliest antiquity by people around the globe. The benefits of restricting energy intake severely for two days a week while eating normally the rest of week has been popularised. However, the evidence for the health benefits of fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting, or derived from experimental studies. Furthermore, periods of prolonged daily fasting may be especially beneficial to improving sensitivity to insulin. However, whether the reduced water consumption and physical activity during ramadan may mitigate these health is less well studied. Therefore, This study tested the hypothesis that prolonged daily fasting, for greater than 12 h in a 24 h cycle, without calorie restriction, reduces hyperinsulinaemia even in the absence of weight loss.Methods. All participants were non-Caucasians males. The study consisted of three phases: phase1:2 visit in the 10 days prior to the start of ramadan, phase 2:3 visits (1 per week) during the 30 days of ramadan and phase 3:1 vist one month after ramadan, when normal patterns of eating and exercising had been resumed. At each study day subjects attended twice, once in the morning (between 08:30 and 10 AM) and once in the afternoon (between 2.00 to 4.30 PM). All subjects completed a questionnair detailing age, smoking habits, medical history, sleeping patterns, dietary intake and training schedule. The studies were approved by National research Ethics Committee and written informed consent was obtained for all participants. 10 subjects completed the study.Weight (Kg) and body composition was measured by electrical bio-impedance (Tanita MC-980 MA) with light cloths at each AM visit. Height (m) was measured on the first visit and BMI was calculated by using formula body weight (kilometres) divided by height (meters) squared. All the participants remained seated for 10 minutes prior to determination of systolic and diastolic blood pressure, and heart rate using an automatic digital blood pressure monitor from the non-dominate arm and mean atrial BP (MAP). blood samples were drawn at all occasions through the ante cubical vein into tubes containing no anti-coagulant or EDTA, separated and stored until analysis. Plasma glucose (mmol/L), serum triglycerides (mmol/L), high density lipoprotein cholestrol (mmol/L), total and direct bilirubin (umol/L), Alanine transaminase (U/L), Aspartate aminotransferase (U/L), urea (mmol/L), uric acid (umol/L), and creatinine (umol/L) concentrations were determined on a chemistry analyser. Insulin (mU/L) concentrations were determined by ELISA. Results are experssed as mean and standard deviattion for normally distributed data and median and iterquartile ranges for skewed data. Significance was defined as P < 0.05.Results. There was significant reduction in body weight during the 2nd and 3rd weeks of ramadan. This weight loss was not sustained in the period immediately following the fasting months as all weight loss was regaind. Body mass index followed the same pattern as body weight. Body fat, both % and mass, decreased soon after the start of fasting (within 2 - 3 days) and was sustaind through the three ramadan testing phases. However, like body weight this loss in body fat was regained in the period immediately after normal eating patterns were resumed.There were no significant changes in muscle mass or body water as a consequence of fasting during Ramadan.There were no significant changes in blood pressure, pulse or basal metabolice rate throughout the entire study.Please (see Table 1) for details.Of note is that all participants were hyperinsulinaemic through the periods of testing prior to and after the cessation of the fasting month. However, during the fasting period insulin levels were significatly reduced. Similar trends were also apparent for alanine transaminase and triglycerides (see Table 2). No changes were seen for all other measured variables. All subjects remained euglycaemic and normotentive.Conclusions. This study shows, for the first time that, prolonged periods of fasting during the day, even without reducing overall daily calorie intake, favours loss of body fat, while preserving muscle mass. This was accompanied by significant improvement in systemic hyperinsulinaemia and indices of liver function.
-
-
-
Corneal Confocal Microscopy Detects Alterations in Corneal Endothelial Cell Morphology in Patients Admitted with Acute Ischemic Stroke
By Adnan KhanBackground The major risk factors for stroke include diabetes, hypertension, smoking, dyslipidemia 1 and metabolic syndrome 2. Endothelial dysfunction is central to promoting vasoconstriction and thrombosis and limited angiogenesis 3 and may also contribute to enhanced plaque vulnerability, triggering plaque rupture, and thrombus formation. There are many methods to assess endothelial dysfunction including brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine and alterations in endothelium dependent dilatation using laser Doppler. We have previously shown significant abnormalities in gluteal resistance vessel endothelium dependent dilatation in patients with obesity 4, diabetes and hypertension 5. Patients admitted with an acute ischemic stroke had reduced forearm flow mediated dilatation and increased circulating levels of P-selectin, a marker of endothelial dysfunction, suggesting widespread vascular abnormalities 6. These measures of endothelial dysfunction are evaluated in vascular territory which is a distance from the brain. Direct imaging of the cerebral blood vessels can identify atherosclerosis 7 and Magnetic resonance imaging can identify silent infarcts, cerebral microbleeds, periventricular white matter hyperintensities and perivascular spaces, which have been shown to predict a higher risk of stroke 8. Subtle alterations in the microstructure of normal-appearing white matter, independent of prevalent vascular lesions also predicts the risk of stroke 9. However, these techniques cannot directly image endothelial cells. We have pioneered corneal confocal microscopy as a rapid non-invasive ophthalmic imaging technique to image the corneal nerves. Whilst we have predominantly demonstrated an abnormality in the corneal nerves in a range of peripheral neuropathies 10, more recently we have shown an abnormality in central neurodegenerative conditions including Parkinson's disease 11 and multiple sclerosis 12. Furthermore, in our recent study we showed that people with acute ischemic stroke also had a reduction in corneal nerve fibers 13. In the present study, we have undertaken corneal confocal microscopy and automated quantification of endothelial cell density, area and perimeter as well as the degree of polymegathism and pleomorphism and related it to corneal nerve morphology and vascular risk factors in a cohort of patients admitted with acute ischemic stroke. Aim Corneal confocal microscopy can identify alterations in corneal endothelial cell morphology and neuronal deficit in patients presenting with an acute ischemic stroke. Methods One hundred and forty six patients admitted with an acute stroke with NGT (n = 62); IGT (n = 34) and T2DM (n = 50) and 18 age-matched healthy control participants underwent corneal confocal microscopy. There was a significant reduction in corneal endothelial cell density and an increase in endothelial cell area and perimeter in stroke patients with NGT (P = 0.002, P = 0.001, P = 0.002), IGT (P = 0.030, P = 0.028, P = 0.06) and T2DM (P<0.001, P<0.001, P = 0.001) compared to controls, respectively, with no significant difference in polymegathism and pleomorphism in stroke patients compared to healthy controls. There was a significant reduction in CNFD, CNBD and CNFL in stroke patients with NGT (P = 0.016, P = 0.001, P = 0.016), IGT (P = 0.007, P = 0.005, P = 0.007) and T2DM (P = 0.002, P = 0.008, P = 0.002) compared to controls, respectively. Diastolic blood pressure correlated with endothelial cell density (P = 0.01), endothelial cell area (P = 0.02) and endothelial cell perimeter (P = 0.01). Endothelial cell density, endothelial cell area and perimeter correlated with corneal nerve fiber density (P = 0.03, P = 0.02, P = 0.02) and corneal nerve fiber length (P = 0.02, P = 0.02, P = 0.023), respectively. Conclusion We show a reduction in corneal endothelial cell density and an increase in size which relates to diastolic blood pressure and corneal nerve loss, independent of glucose tolerance status in patients with an acute stroke. CCM allows rapid non-invasive imaging of endothelial cells to enable risk stratification of patients with stroke. References 1. Shuaib A. Alteration of blood pressure regulation and cerebrovascular disorders in the elderly. Cerebrovasc Brain Metab Rev. 1992;4:329-345 2. Heymann EP, Goldsmith D. Best approaches in the battle against globesity? Learning lessons from our experience tackling hiv-aids and tobacco smoking. JRSM short reports. 2012;3:45 3. Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. International journal of biological sciences. 2013;9:1057 4. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. Effects of bariatric surgery on human small artery function: Evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. Journal of the American College of Cardiology. 2013;62:128-135 5. Malik RA, Schofield IJ, Izzard A, Austin C, Bermann G, Heagerty AM. Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus. Hypertension. 2005;45:264-269 6. Blum A, Vaispapir V, Keinan-Boker L, Soboh S, Yehuda H, Tamir S. Endothelial dysfunction and procoagulant activity in acute ischemic stroke. Journal of vascular and interventional neurology. 2012;5:33 7. Imam YZ, D'Souza A, Malik RA, Shuaib A. Secondary stroke prevention: Improving diagnosis and management with newer technologies. Translational stroke research. 2016;7:458-477 8. Debette S, Markus H. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis. British Medical Journal. 2010;341:c3666 9. de Groot M, Verhaaren BF, de Boer R, Klein S, Hofman A, van der Lugt A, et al. Changes in normal-appearing white matter precede development of white matter lesions. Stroke. 2013;44:1037-1042 10. Alam U, Jeziorska M, Petropoulos IN, Asghar O, Fadavi H, Ponirakis G, et al. Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy. PloS one. 2017;12:e0180175 11. Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, et al. Small fiber neuropathy in parkinson»s disease: A clinical, pathological and corneal confocal microscopy study. Parkinsonism and Related Disorders. 2015;21:1454-1460 12. Petropoulos IN, Kamran S, Li Y, Khan A, Ponirakis G, Akhtar N, et al. Corneal confocal microscopy: An imaging endpoint for axonal degeneration in multiple sclerosis. Investigative Ophthalmology & Visual Science. 2017 13. Khan A, Akhtar N, Kamran S, Ponirakis G, Petropoulos IN, Tunio NA, et al. Corneal confocal microscopy detects corneal nerve damage in patients admitted with acute ischemic stroke. Stroke. 2017:STROKEAHA. 117.018289
-
-
-
Large Scale Omics Analysis of Type 2 Diabetes in the Qatari population
Authors: Noha A. Yousri, Khalid A. Fakhro, Ronald G Crystal and Karsten SuhreBackground: The prevalence of Type 2 Diabetes (T2D) in Qataris has been recently recorded (as to the Qatar Bio Bank) to be around 14-15%. T2D associated macro- and micro-vascular complications leading to retinopathy, neuropathy, nephropathy, as well as cardiovascular complications are among the most known factors leading to death. Both genetics and environmental/life style factors play roles in the pathophysiology of T2D. The advent of the Qatar Genome Project and whole genome sequencing of the Qataris will provide a wealth of genomic information on several diseases inherent in the Qataris and specifically high prevalent ones as T2D and its complications. Profiling other “omics” data as gene expression, metabolomics, proteomics, and epigenetics among others became imperative for unraveling the complex nature of T2D and the effect of both genetic and environmental factors. Objectives: In this study we focus on integrating metabolomics and genomics data for identifying their associations to T2D using nearly 1000 Qatari samples. We achieve that in the following main steps: 1-Identifying associations between metabolites and exome variants (metabolic Quantitative Trait Loci (mQTL)) in 1000 Qataris for the sake of identifying mQTLs (metabolic Quantitative trait loci) linked to both common and rare variants in Qataris. 2-Identifying T2D associated metabolites and the pathways enriched in those metabolites. 3- Investigating the associations of T2D to genes/exome variants linked to T2D through the identified mQTLs (step 1). Materials and Methods: Genomics Data: 1000 samples were collected from Qatari individuals (50% with T2D), where DNA was extracted and used for both whole exome sequencing (n = 614) and genotype arrays (n = 382)(4 samples were removed after quality control, leading to 996 samples in total). Exome and array data were imputed after being filtered (MAF> = 0.05, pHWE>10-6, genotype call rate > = 98%) based on phased 108 Qatari whole genomes as a reference panel, using shapeit and Impute2 software packages. A total of 1.6 million variants from the imputed exome were used for discovery analysis of the mQTLs and the array data was used for replication. Metabolomics Data: Serum samples for the 1000 samples were used for profiling metabolomics using a recent advanced Metabolon platform (DiscoveryHD4). This platform utilized a Waters ACQUITY ultra-performance liquid chromatography (UPLC) and a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. A total of 1303 metabolites were measured on that platform, and we were only left with a total of 826 metabolites (including 249 unknown metabolites) for the analysis after quality control (missing values < 20%, and outliers removed). Association Analysis: Linear regression models were used for computing associations between Metabolites and SNPs, as well as between metabolites and T2D after correcting for covariates. Results For metabolomics – Exome wide associations [Yousri et. al 2017], we discovered and replicated 21 unique mQTLs associated with common variants (MAF > 5%) and discovered another 12 mQTLs associated with rare variants using burden tests and single variant analysis. Overall, 45% of the discovered loci are novel ones. We also replicated 19% of the known mQTLs in European populations using the discovery cohort. Regarding metabolomics of T2D, we identified 190 metabolites associated with T2D, spanning pathways of fatty acid metabolism, phospholipids, sphingolipids, phenylalanine and tyrosine metabolism among others, and where 40% of the metabolites were newly identified (new to our previously reported T2D metabolites in different biofluids [Yousri et al 2015]). We also identified several associations between genes known to be associated with T2D and T2D associated metabolites. In summary, we have both identified mQTLs from large scale metabolomics (m = 826) and whole exome sequencing, and identified T2D metabolites using a large sample set (∼1000 samples), and used those to reveal the links between an intermediate phenotype – metabolite - and the genes/variants known to be associated with T2D. This is considered the first time this study is done in the Qataris integrating omics data on a large scale. References: [Yousri et. al 2017] Noha A. Yousri, Khalid A. Fakhro, Amal Robay, Juan L. Rodriguez-Flores, Robert P. Mohney, Hassina Zeriri, Tala Odeh, Sara Abdul Kader, Eiman Aldous,Gaurav Thareja, Manish Kumar, Alya Al-Shakaki, Omar M. Chidiac,Yasmin Mahmoud, Jason G. Mezey, Joel Malek,Ronald G. Crystal5, Karsten Suhre. “Whole Exome Sequencing identifies common and rare variant Metabolic Quantitative Trait Loci in a Middle Eastern Population”. Accepted in Nature Communications. [Yousri et al 2015] Noha A. Yousri, Dennis O. Mook-Kanamori, Mohammed M. El-Din Selim, Ahmed H. Takiddin, Hala Al-Homsi, Khoulood A.S. Al-Mahmoud, Edward D. Karoly, Jan Krumsiek, Kieu Thinh Do, Ulrich Neumaier, Marjonneke J. Mook-Kanamori, Jillian Rowe, Omar M. Chidiac, Cindy McKeon, Wadha A. Al Muftah, Sara Abdul Kader, Gabi Kastenmüller, Karsten Suhre, “A systems view of Type 2 Diabetes-associated metabolic perturbations in saliva, blood and urine at different time-scales of glycemic control”, Diabeteologia, August 2015.
-
-
-
Management of Chronic Diabetic Foot Ulcers at Primary Care Level in Qatar :An Alternative Paradigm in Wound Healing
More LessBACKGROUND AND AIMS: Chronic Diabetic footulcers (CDFU) are associated with increased morbidity, mortality especially indeveloping countries. This cohort study assess the efficacy (CDFU)management at primary care & identifypredictive criteria of failure. METHODS: We conducted a 5-year retrospective cohort study withprospective long-term follow-up of all patients with (CDFU) who presented to Umgwalinah Health Centre, Doha, Qatar. Average follow-up was 1 year. Failure of healing of (CDFU) was themain outcome measure.Independent predictor variables were selected by logisticregression analysis. RESULTS: A total of 126 patients with diabetes were managed forvarious foot lesions as follows. Five patients (4%) of 126 underwent immediate amputation. Primary care led approach was successful for 91(92.86%) of 98 neuropathic ulcers, 3(30%) of 10 neuro-ischemic ulcer, 2(66%) of 3 Charcot foot ulceration, 4(100%) of 4 patients with second degree burns & 6(100%) of 6 traumatic foot ulceration or (P<.001,chi2 for trend).Independent factors predictive of failure to heal were presence of osteomyelitis(odds ratio [OR] = 1.6, 95% confidence interval [CI], 1.0-1.3), increased Hemoglobin A1C level (OR = 1.002; 95% CI, 1.2-1.3), severe peripheral vascular disease(OR = 1.0, 95% CI,1.0-1.03),prior hospitalization for(CDFU) (OR = 1.4; 95%CI, 1.2-1.6) & gangrenous lesion(OR = 1.7; 95% CI,1.3-2.1). No side effects were reported and there was a high level of satisfaction (patients and staff). CONCLUSIONS: Primary care based management of (CDFU) is efficacious, safeand acceptable. These findings may lead to a substantial reduction in the costof (CDFU) in the third world. Future comparative studies utilizing randomized controlled trials must be conducted in order to accurately assess the efficacy of primary care in managing (CDFU).
-
-
-
Antidiabetic and Toxicological studies of ethylacetate and nhexane fractions of Gymnema sylvestre
More LessGymnema sylvestre is a medicinal plant that is used in the folkloric treatment of diabetes mellitus and the management of its complications. This study was aimed at evaluation of antidiabetic and toxicological effects of ethylacetate and n-hexane fractions of Gymnema sylvestre whole plant. Diabetes was induced in Swiss albino rats by single intraperitoneal administration of 110 mg/kg bodyweight of alloxan monohydrate. Rats in their respective groups were orally administered 100, 300 and 600 mg/kg bodyweight of ethylacetate and n-hexane fractions of the plant daily while the standard drug group received 100 mg/kg bodyweight of metformin. The treatment lasted for fourteen days and on the fifteenth day, animals were anaesthetized and euthanized. Blood samples were collected by carotid puncture for biochemical analysis. In the subchronic toxicological aspect of the study, rats in their respective groups were administered 100, 300, 600 mg/kg bodyweight of the extracts daily for twenty one days and the experiment was terminated on the twenty second day. All the extracts were able to reduce the blood glucose of diabetic rats with 300 mg/kg bodyweight of ethylacetate fraction having higher reduction at 82%. All diabetic rats showed decrease in bodyweight when compared with normoglycemic group. There was significant (p<0.05) reduction in the total cholesterol, triacylglycerol, low density lipoprotein and a concomitant increase in the values of high density lipoprotein in all treated groups when compared with diabetic untreated (negative control). The activity of serum liver enzymes (?- glutamine transpeptidase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) and bilirubin significantly decreased (p<0.05) compared with the diabetic untreated group. Levels of total protein in the treated groups did not differ from the normoglycemic group, while there was a reduction in the concentration of albumin of ethylacetate fraction in a dose dependent manner. All treated groups gave urea and creatinine values that showed no significance differences (p>0.05) with the normoglycemic group. The electrolytes showed significant differences (p<0.05) in all treated groups when compared with the normoglycemic group. There was significant difference (p<0.05) in all the biochemical parameters carried out on the subchronic toxicity test with rats administered ethylacetate and n-hexane fractions of G. sylvestre. The hematological parameters (red blood cell, mean cell volume, mean corpuscular hemoglobin concentration, packed cell volume, hemoglobin) showed no significant difference but a non significant difference in the white blood cell of rats administered with the extract. Therefore, extracts of G. sylvestre might be useful for management of diabetes mellitus and other abnormalities associated with this metabolic disorder
-
-
-
Generation of a Novel Population of Pancreatic Multipotent Progenitor Cells Expressing NKX61
Authors: Essam Abdelalim, Idil I. Aigha, Ahmed K. Elsayed and Bushra MemonDiabetes is a metabolic disease caused by the loss or impaired function of insulin-producing pancreatic β-cells. Different therapeutic strategies aim to restore the endogenous production of insulin rather than the cornerstone insulin injections treatment. Human pluripotent stem cells (hPSCs) have been proposed as an unlimited source for cell-based therapy of diabetes through the directed differentiation into functional pancreatic β cells. Step-wise differentiation protocols based on developmental biology of pancreas, have led to the generation of insulin-producing β cells. However, the majority of the cells produced were poly-hormonal as they expressed other hormones in addition to insulin and have failed to respond when challenged with glucose. The coordinate expression of particular transcription factors (TF) in distinct stages governs the differentiation of hPSCs into insulin β cells. Pancreatic and duodenal homeobox protein (PDX1) is a crucial TF required for pancreas development. On the other hand, homeobox protein NKX6.1 is a potent bi-functional TF that is essential for β cells maturation, proliferation and insulin metabolism. The dual expression of PDX1 and NKX6.1 during multipotent progenitor cell (MPC) stage is vital for guiding the cells towards functional β cells lineage. However, cells expressing PDX1 but lack NKX6.1 expression tend to take the poly-hormonal path. This guided the differentiation protocols to focus on enriching MPC population co-expressing PDX1 and NKX6.1. The aim of this study was to further explore different MPC populations in terms of PDX1/NKX6.1 expression. We used two different differentiation protocols to differentiate hESCs and hiPSCs into MPCs. The mRNA and protein expressions of the generated MPCs were analyzed using immunocytochemistry, RT-PCR, and flow cytometry. Our results showed that hPSCs were successfully differentiated into the conventional (PDX1+/NKX6.1+) and (PDX1+/NKX6.1-) MPC populations. The efficiency of differentiating hPSCs into PDX1+/NKX6.1+ MPCs has varied between the two used protocols. Immunofluorescence staining has unveiled the generation of a novel population that expressed NKX6.1 independently of PDX1 (PDX1-/NKX6.1+) in both hESCs and hiPSCs. This is surprising considering that PDX1 was reported to bind to the promoter of NKX6.1 gene and is needed for NKX6.1 expression. Furthermore, using our optimized protocol, this uncharacterized subset of MPCs was enriched and found to exhibit a pattern of three-dimensional (3D) aggregates that were consistently (PDX1-/NKX6.1+) and surrounded by either (PDX1+/NKX6.1+) or (PDX1+/NKX6.1-) MPCs. To understand and characterize this unique population, we examined the expression of other TFs including endocrine precursors markers Chromogranin A (CHGA) and NKX2.2. CHGA was found to be expressed in the same areas that were positive for NKX6.1 and PDX1. However, the 3D structures that were PDX1-/NKX6.1+ did not co-express CHGA. On the contrary, few cells of these 3D aggregates co-expressed NKX2.2, suggesting that this population may have an undefined role in the development of MPCs into endocrine progenitors. These findings showcase a novel population of NKX6.1 expressing MPCs that did not require PDX1 expression at this stage. Moreover, this population may retain an alternative path towards pancreatic islet cells development that is independent of PDX1. A thorough characterization of this population is needed to explore the regulatory gene network controlling their lineage specification.
-
-
-
Enhancement of differentiation of multipotent pancreatic β cell precursors from human embryonic stem cells
Authors: Essam Abdelalim, Bushra Memon, Manale Karam and Sara Al-KhawagaScalable production of human pluripotent stem cell (hPSC)-derived β cells in vitro would greatly facilitate transplantation therapy and drug discovery for treating diabetes. Employing step-wise differentiation protocols, hPSCs can be differentiated through consecutive stages of endoderm, foregut, pancreatic and endocrine progenitors to ultimately give insulin secreting β cells. Pancreatic progenitors co-expressing the two key transcription factors (TFs), PDX1 and NKX6.1, are recognized as the indispensable precursors of functional, mono-hormonal β cells. Here, we established an optimized protocol for maximizing PDX1+/NKX6.1+ co-positive pancreatic progenitors from hESCs in monolayer culture and increasing their proliferative capacity. Our technique of dissociating densely formed endodermal cells and re-plating them in lower densities on fresh matrigel matrix followed by an augmented duration of retinoid and FGF10 signaling strikingly increased the expression of NKX6.1, which is exclusive only to β cells amongst all endocrine cells. This high induction of NKX6.1 resulted in an increased proportion of PDX1+/ NKX6.1+ population, generating up to >90% PDX1+/ NKX6.1+ co-positive progenitors in monolayer, higher than previously published protocols. In contrast to multiple studies showing negligible induction of NKX6.1 at lower densities, we provide evidence that higher folds of NKX6.1 can be induced in dissociated cells re-plated lower densities compared to aggregations in non-dissociated culture if the duration of retinoid and FGF signaling is prolonged. Our optimized protocol enhanced pancreatic differentiation efficiency by up-regulating pancreatic progenitor TFs such as PDX1, SOX9, HNF6 and FOXA2 and increased the mRNA levels of endocrine TFs such as NEUROG3, NKX2.2 and NEUROD1. Additionally, we show that manipulating cell-cell attachment following endoderm generation in vitro during pancreatic differentiation dramatically inhibited alternate hepatic fate specification by down-regulating hepatic markers like AFP and ALB expression in our optimized protocol in comparison to recently published protocols for generating pancreatic progenitors. Notably, cell cycle and BrdU incorporation assays revealed that our method increased the proliferative capacity of pancreatic progenitors throughout the differentiation stages by increasing the fraction of cells entering S phase of cell cycle and a comparative increase in Ki67 expression, the proliferation marker. As a result, we obtained >70% Ki67+ /SOX9+ pancreatic progenitors in monolayer confirming an increased self-replicating capacity of the generated PDX1+/ NKX6.1+ progenitors. Furthermore, using our optimized protocol for pancreatic differentiation, we were able to enrich a novel and uncharacterized NKX6.1+ /PDX1- population, devoid of Chromogranin A (CHGA) expression, which are therefore proposed to be more mature precursors of β cell. This population re-arranged themselves in embedded, highly compact three-dimensional structures that showed high expression of Ki67. Continuation of our optimized protocol into endocrine differentiation stage validated the ability of our PDX1+/ NKX6.1+ to generate NGN3+/ NKX6.1+ co-positive endocrine progenitors in vitro with a high expression of CHGA and NKX2.2. Therefore, here we show that manipulating the cellular density, cell-cell attachment and cues from extracellular matrix plays a major role in improving pancreatic differentiation efficiency and proliferation thereby providing a cost-effective method for generating pancreatic progenitors in vitro in adherent culture. Indeed, our novel method for maximizing PDX1+/ NKX6.1+ progenitors from hPSCs in monolayer culture could serve as a source of highly proliferative pancreatic progenitors aiding scalable production of functional β cells in vitro.
-
-
-
Impact of a Collaborative Pharmaceutical Care Service among Patients with Diabetes in Qatar Petroleum Healthcare Center Dukhan: A Multiple Time Series Study
Authors: Ahmed Awaisu, Sara Abdulrhim, Rana Saleh, Mohamed Abdelazim, Hend Alraey, Ahmed Babiker and Nadir KheirBackground: Diabetes mellitus is a highly prevalent non-communicable disease worldwide. The prevalence of diabetes in Qatar exceeds the prevalence of diabetes in the Middle East and North Africa region and the globe. Similarly, diabetes-related complications and mortality are dramatically increasing worldwide. Poor health outcomes and debilitating consequences can result from inadequate control of diabetes. Previous studies have demonstrated the benefit of pharmaceutical care services on outcomes of diabetes. No studies were done in Qatar regarding this issue. Therefore, the objectives of this study were to: (1) characterize the clinical profile of patients with diabetes attending an ambulatory care clinic at Qatar Petroleum (QP) Medical Center including diabetes-related comorbidities and complications; (2) evaluate the impact of a Comprehensive Pharmaceutical Care Service (CPCS) on glycemic control [glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)]; (3) evaluate the impact of the CPCS on diabetes comorbidities including lipid profile [low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC)], systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) and; (4) classify the drug-related problems (DRPs) identified by pharmacists during the follow-up period. Methods: This was a multiple time series, observational, retrospective, pre-post study among patients attending diabetes clinic at QP Medical Center in Dukhan. Primary clinical outcome measures including HbA1c, FPG, weight, BMI, SBP, DBP, and lipid profile were measured at baseline, 6 months, and 12 months after receiving the CPCS through a retrospective chart review of electronic medical records for the year 2016. The secondary outcome measure, the types of DRPs identified by pharmacists, was collected over the period of 12 months of initiating the CPCS and categorized into a predetermined classification system. Data analyses were performed using IBM SPSS® version 23.0. Primary clinical outcome measures were analyzed inferentially using Repeated Measure ANOVA to determine the impact of the intervention. Sociodemographic characteristics, basic clinical characteristics, baseline and current medications regimens, and types of DRPs identified by pharmacists were analyzed descriptively using frequencies, percentages and means as appropriate. Results: A total of 96 eligible patients with diabetes were included in the study. CPCS significantly improved the following parameters from baseline to 6 and 12 months: HbA1c (8.5%, 7.4%, 7.1%, respectively; P <0.001), FPG (154.1 mg/dL, 115.4 mg/dL, 112.8 mg/dL, respectively; P <0.001), weight (79.9 Kg, 78.3 Kg, 76.9 Kg, respectively; P <0.001), BMI (29.1 Kg/m2, 28.5 Kg/m2, 28.1Kg/m2, respectively; P <0.001), SBP (140.2 mmHg, 129.1 mmHg, 125.3 mmHg, respectively; P <0.001) and DBP (84.7 mmHg, 79.5 mmHg, 76 mmHg, respectively; P <0.001). However, no significant reductions from baseline to 6 and 12 months were observed in LDL-C (2.7 mmol/L, 2.8 mmol/L, 2.7 mmol/L, respectively; P = 0.702), HDL-C (1.2 mmol/L, 1.2 mmol/L, 1.3 mmol/L, respectively; P = 0.551), TG (1.6 mmol/L, 1.7 mmol/L, 1.7 mmol/L, respectively; P = 0.728), and TC (4.3 mmol/L, 4.3 mmol/L, 4.1 mmol/L, respectively; P = 0.101). The most prevalent three DRPs identified were lack of understanding of the medication (39.8%), inappropriate dose, form, schedule, route, or method of administration (17.3%), and actual and potential adverse events (14.3%). Conclusion: The provision of CPCS in a primary healthcare setting in Qatar improves clinical outcomes in patients with diabetes over a 12-month follow-up period. Future studies are needed to determine the long-term outcomes of CPCS.
-
-
-
NonInvasive Wearable Sensors to detect onset of hypoglycemia: A Literature Review
Authors: Karim Zahed, Farzan Sasangohar, Yibo Zhu, Ranjana Mehta, Madhav Erraguntla, Mark Lawley and Khaled QaraqeIntroduction: Hypoglycemia is a prevalent condition where diabetic patients experience low blood glucose. There are approximately 300 million diabetic patients in the world; at least 30 million of those are in the United States. Diabetic patients facing hypoglycemia continue to grow but the condition worsens as patients lose awareness the more episodes that occur. Mild hypoglycemia is characterized as blood glucose below 70mg/dl and severe as blood glucose below 40mg/dl (Kalra et al., 2013). Severe hypoglycemia may cause loss of patient's awareness and in some cases fatality. Loss of awareness leads to a 6-fold increase in the risk of death. While in most cases hypoglycemia is treated through medication and diet (e.g. fast-acting carbohydrates), a popular technology among diabetic patients; especially those with hypoglycemia unawareness; is continuous glucose monitors (CGM). While CGMs have shown promise, these devices are expensive, invasive, and not always accurate throughout the day (Bay et al., 2013). Hypoglycemic events are associated with several signs and symptoms such as fatigue, sweating, and pale skin, but tremors seem to be a prevalent symptom as well. One study has reported that around 20% of hypoglycemic patients stated that trembling is the first symptom they notice indicating low blood sugar (Muhlhauser, 1991), and another showed that 77.5% of diabetic patients who are aware of their symptoms experience tremors (Berlin, 2005). Our research aims at investigating the efficacy of using hand (or leg) tremor to predict the early onset of hypoglycemic events. Work is in progress to design and develop a non-invasive sensor-based wearable system that detects hypoglycemic tremor with high sensitivity and specificity. Method: A systematic review of literature is in progress to search variety of medical and engineering databases to identify research related to hypoglycemia detection, wearable sensors, and tremor. The studies considered are those pertaining to diabetic patients who have been assessed for the symptoms of hypoglycemia and the sensors used in order to predict a hypoglycemic episode. One of the main objectives of the study is to understand hypoglycemia and its symptoms, and to document technological interventions, related detection methods and sensors, as well as their shortcomings and opportunities. We hypothesize that tremor has not been used for hypoglycemia detection. The research is motivated by the preliminary review evidence that suggests current sensor-based technologies to address diabetes and hypoglycemia suffer from low patient engagement and satisfaction due to intrusiveness, low accuracy, and price. Results: While the review is in progress, we expect to have completed the search by January and plan to present the comprehensive findings at the conference. Our preliminary findings suggest a large research gap in non-intrusive technologies and methods to detect hypoglycemic events. While a frequency band of 10-14 Hz in the wrist for hypoglycemic tremors has been suggested in the literature (Rana & Chou, 2015), there is very little research done on utilizing this phenomenon to predict hypoglycemia. Most research relies on other symptoms such as skin conductance and body temperature which have been shown to cause inaccurate predictions (Howsmon & Bequette, 2015). In understanding the tremors, it is important to consider at the time the tremors start to occur in relation with particular activities, food consumption, and blood sugar; as well as the location of these tremors and their prevalence. The current review found studies that assess and promote user-centered design, and the usability of wearable sensors. This includes usability studies, human factors and FDA requirements, and other recommendations to be incorporated into developing a wearable sensor. Wide range of factors related to patient comfort and usability were identified, they include optimizing between battery life and data processing, size, location on the body. These findings are in line with other studies such as those done on wearable sensors for detection of Parkinson's disease (Rigas et al., 2012). Despite these preliminary findings, comprehensive guidelines to design for wearability had not been offered. Based on these and upcoming findings a taxonomy for design criteria for wearability will be presented. Conclusion: Diabetes is a growing epidemic and the occurrence of hypoglycemia for diabetic patients is prevalent and potentially fatal. Detecting the onset of hypoglycemia is vital and tremors seem to be a viable symptom. Our preliminary findings from a systematic literature review suggest a general gap in technological interventions for early detection and recognition of hypoglycemic events. In particular, our current findings show that tremor detection technologies have not been utilized in this domain. Sensors assessing tremor frequency could be an alternative approach to current sensors in the market and may contribute to non-intrusive, high accuracy and low cost solutions. This review will inform a taxonomy of design considerations for non-intrusive wearable technologies. Our future work aims at addressing this gap by utilizing a user-centered design of a wearable device to detect the early onsets of hypoglycemic events by measuring tremor.
-
-
-
Hypoglycemic and Cardioprotective Effects of Methanol Extracts of Gymnema Sylvestre Plant and Annona Senegalensis Carpels Used in the Folkloric Treatment of Diabetes
More LessThe epidemic of diabetes has major health and socioeconomic impacts especially in developing countries, and subjects with diabetes have increased risk of disease affecting the heart, blood vessels, eyes, kidneys and nerves. Whole Gymnema sylvestre plant and Annona senegalensis carpels are used in the folkloric treatment of diabetes mellitus and the management of its attendant complications. Diabetes was induced in Swiss albino rats by single intraperitoneal administration of 11 mg/kg bodyweight of alloxan monohydrate and rats with blood glucose ≥ 206 mg/dl were considered diabetic. Rats in their respective groups were orally administered 100, 300 and 600 mg/kg bodyweight of extracts of either Annona senegalensis carpels or Gymnema sylvestre daily for fourteen days while the standard drug group received 100 mg/kg bodyweight of metformin for the same period. The normoglycaemic (positive control) and the diabetic untreated (negative control) groups received 0.5 ml normal saline. The animals were euthanized on the 15th day and blood samples were collected by carotid puncture for biochemical analysis. The 600 mg/kg bodyweight dose of Gymnema sylvestre and 300 mg/kg bodyweight dose of Annona senegalensis carpels respectively reduced the blood glucose of diabetic rats by 76.45 % and 72.01 %. All treatment groups of Gymnema sylvestre gave urea and creatinine values that showed no significance differences (p>0.05) with the normoglycemic (positive control) group while urea and potassium ion (K+) concentrations at 600 mg/kg bodyweight of Annona senegalensis carpels extract reduced significantly as the blood glucose progressively declined. Chloride ion (Cl− ) concentrations in the treatment groups for both extracts did not differ from the normoglycemic (control) group, while there was a reduction in the concentrations of potassium ion (K− ) of 100 and 300 mg/kg bodyweight treated groups of Gymnema sylvestre extract. There was also a reduction in the concentration of sodium in all treated groups when compared with the normoglycemic group. The concentrations of total cholesterol, triacylglycerol, low density lipoprotein also reduced regressively as the treatment days progressed and a concomitant increase in the values of high density lipoprotein in all treated groups for both extracts when compared with diabetic untreated (negative control). The crude methanol extracts of Gymnema sylvestre and Annona senegalensis carpels were able to lower the blood glucose of diabetic rats and ameliorate the attendant hyperlipidemic effect associated with diabetes.
-
-
-
Endothelila based cardiac regeneration
Authors: Arash Rafii, Jennifer Pasquier, Khaled Machaca, Raphael Courjaret and Charbel Abi KhalilBackground - The regenerative ability of the heart is very low, making patients with myocardial damage potential candidates for cell-based regenerative therapy. Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes (CMs). While the quantity of CMs obtained is no longer a limitation in current differentiation protocols, their inotropy needs to be improved.We have creaated in Doha since the last 10 years a unique plafrm based on endothelial feeder as an instructive niche for organ regeneration. We have been ablse so for to demonstrate efficient regeneration in liver lung and HSCs regeneration. Here we hypothesized that we could improve maturation of CMs and facilitate electrical interconnections by creating a mixture of cell types that more closely resembles heart tissue - i.e. containing both endothelial cells (ECs) and cardiomycocytes. Using our unique endothelial platfrom we demonstrated an increased in differentiated functional CM. CMs formed under these conditions displayed a higher rate of contraction. The co-culture with endothelial cells led to synchronized beating relying on the endothelial network as illustrated by the loss of synchronization upon the disruption of endothelial bridges. Hence we created a unique platfrom allowing to expand functional cardiomycocytes that could be potentially used in cell therapy protocol. Our research promotes the concept of organoid based cell therapy.
-
-
-
Screening for diabetic retinopathy with a deep learning network: Evaluation of retinal images from the Qatar Biobank
Authors: Patrick De Boever, Bart Elen, Arnout Standaert and Rayaz A MalikDiabetic retinopathy (DR) is the leading cause of impaired vision and blindness in working age adults. Regular eye screening is advised to prevent progression to blindness. However, screening programs are labor- and capital-intensive and suffer from limited access to trained professionals. Artificial intelligence has been employed to develop algorithms for automated classification of retinal images. We developed an ensemble model of two deep convolutional neural networks to score DR in fundus images. The model was trained using tens of thousands images from a public database and allows the determination of DR stage, as well as referable DR. The model was validated on 1748 fundus images from the Messidor-2 database. All 190 patients with referable DR were successfully detected by our deep learning (DL) model (sensitivity 100%, 95%CI 98.1%-100%). The model labelled 444 of the 684 diabetes patients without referable DR accordingly (specificity 65.0%, 95%CI 61.2%-68.5%). The DL model was further evaluated on retinal images from the Qatar Biobank. Images from 740 individuals enrolled in the Qatar Biobank were received. Image quality was poor in 72 individuals leaving 668 individuals with manually graded images which were independently analyzed using the DL model. The model scored the DR class with an accuracy of 0.88 and a precision of 0.95. Forty-two individuals (6.3%) have some form of DR and referable DR was identified in twenty-six individuals. The model for referable DR had an accuracy of 0.90 and a precision of 0.97. In conclusion, our DL model has been successfully tested on fundus images from the Qatar Biobank. The Automated Retinal Image Analysis System (ARIAS) is promising in relation to supporting medical professionals to undertake cost-effective screening, especially in the context of large population screening programs.
-
-
-
Stress Granules as a possible regulator of pluripotent stem cell self renewal and differentaition
In cells subjected to environmental stresses, such as oxidative stress and heat shock (HS), dynamic ribonucleoprotein aggregates, known as Stress Granules (SGs)), are formed as a part of the cell response program. Different types of stresses control pluripotent stem cell (PSCs) ability to self renew and differentiate, indicating the possible role of SGs in regulating stem cell fate. In this study we compared the effects of oxidative (sodium arsenite (SA) and hydrogen peroxide (H2O2)) and thermal (Heat Shock) stresses on SG formation in human induced (hi) PSCs. Our aim was to examine whether these granules paly a role in regulating PSC self-renewal and differentiation. Our data showed that not all stressors induce SG formation in hiPSCs. Increasing SA concentartions, progressively increase the number of cells showing SGs, however, iPSCs treated with H2O2 exhibited no SG formation even with higher concentrations or longer periods of incubation. On the other hand, no granules were observed in cells kept at 37oC or exposed to mild HS (40oC) treatment, whereas at higher temperatures of 42oC, 100% of the cells formed SGs. Molecular analyses of the granules formed in iPSCs in response to stress conditions showed that they (i) contain the well-known SGs proteins markers (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), (ii) are present in the cytoplasm in a physical attachment to processing bodies (PBs), and (iii) are disassembled after the removal of the stress. This data confirm that these iPSCs granules are per se SGs. In addition, the formation of SGs was associated with the stimulation of eIF2α phosphorylation in hiPSCs after SA and HS, but not H2O2, which confirm the stimulation of the stress response program. To test whether pluripotent marker proteins are recruited to SGs, we perform an initial screening for several pluripotent markers and confirmed that LIN28A and L1TD1 were SG markers and identified DPPA5 as a novel pluripotent marker that was weakly recruited to SGs. Altogether, our data introduce new aspects of how hiPSCs respond to adverse environmental conditions and identify SGs as a possible regulator of pluripotent stem cell self renewal and differentiation.
-
-
-
Suppression of adipocyte hyperplasia through SIRT1mediated inhibition of cMyc function
More LessYasser Majeed1, Aisha Madani1, Muneera Vakayil1, Maha Agha1, Houari Abdesselem2, Mohamed ElRayess3, Moataz Basha4, Nasrin Mesaeli1, Michael Bonkowski5, David A Sinclair5, Nayef A. Mazloum1 1. Weill Cornell Medicine-Qatar, Doha, Qatar 2. Qatar Biomedical Research Institute, Doha, Qatar 3. Anti-Doping Lab-Qatar, Doha, Qatar, 4. Hamad Medical Corporation, Doha, Qatar 5. Harvard Medical School, Boston, MA, USA. Global estimates from the World Health Organization (WHO) suggest that obesity has approximately tripled since 1975 and that over 600 million adults and 300 million children/adolescents were obese. Obesity is a major risk factor for Type 2 Diabetes (T2D) and associated disorders that affect the cardiovascular system. Insulin resistance, insufficient insulin secretion and increased blood glucose levels (hyperglycemia) are characteristic features of T2D. Together with other cardio-metabolic complications observed in T2D, hyperglycemia results in vascular disease and increased morbidity and mortality. There is therefore a worldwide health impact of T2D and its complications. Locally, the incidence of obesity and T2D in Qatar ranks among the highest in the world and is a serious public health burden. Genetic predisposition and environmental factors such as intake of calorie-rich food and a sedentary lifestyle make significant contributions to the obesity epidemic. White adipose tissue (WAT) plays a key role in the pathophysiology of obesity and its associated co-morbidities. WAT is distributed either subcutaneously or within different depots in the intra-abdominal cavity surrounding or near vital organs (viscera). WAT mass expansion observed in obesity is due to enlarged fat cell volume (hypertrophy) and increased cell number (hyperplasia). Hence, understanding how WAT function is dysregulated is essential to understanding the pathophysiology of obesity and designing improved therapeutics to treat obesity and its metabolic complications. There is little known about the molecular mechanism that drives adipocyte hyperplasia in obesity. The NAD-dependent protein deacetylase sirtuin-1 (SIRT1), a master regulator of mammalian metabolism, maintains proper metabolic functions in many tissues counteracting obesity. Our laboratory has shown that differentiated adipocytes are hyperplastic when the expression of SIRT1 is stably reduced in mouse 3T3-L1 preadipocytes. This phenotype is concomitant with altered adipocyte metabolism and increased inflammation. We also show that SIRT1 is critical in the regulation of proliferation of preadipocytes. By employing quantitative proteomics studies, we provided evidence that the molecular pathway downstream of the c-Myc proto-oncogene is affected to drive enhanced proliferation in SIRT1-silenced preadipocytes cells. Our data suggest that c-Myc is transcriptionally activated upon SIRT1 reduction leading to lower levels of p27 (cyclin-dependent kinase inhibitor) and the activation of the CDK2 (cyclin-dependent kinase 2). Remarkably, differentiated SIRT1-silenced preadipocytes show enhanced mitotic clonal expansion (MCE) phenotype along with reduced levels of p27, as well as elevated levels of c-Myc and the adipogenesis transcription factor C/EBPβ. c-Myc activation and enhanced proliferation phenotype were also observed to be SIRT1-dependent in mouse embryo fibroblasts (MEFs) and human SW872 preadipocytes. Interestingly, the stable reduction of both SIRT1 and c-Myc expression in 3T3-L1 preadipocytes did not lead to the adipocyte hyperplasia phenotype, which further confirms that SIRT1 suppresses adipocytes hyperplasia through c-Myc inhibition. Current studies are focused on investigating the in vivo relevance of Sirt1-c-myc interaction in mouse models of diet-induced obesity. We are also isolating preadipocytes from WAT collected from insulin sensitive (IS) and insulin resistant (IR) obese subjects to evaluate differences in their proliferation rates and adipogenic potential and to understand if these might be linked to altered SIRT1 and C-Myc functions. Better understanding of the molecular mechanisms of adipocyte hyperplasia will open new venues towards understanding obesity.
-